20.500.12556/RUL-153999 Targeting the formation of estrogens for treatment of hormone dependent diseases–current status Local formation and action of estrogens have crucial roles in hormone dependent cancers and benign diseases like endometriosis. Drugs that are currently used for the treatment of these diseases act at the receptor (i.e., they interfere with the hormone receptor) and at the pre-receptor levels, targeting the local formation of estrogens. Since 1980s the local formation of estrogens has been targeted by inhibitors of aromatase that catalyses their formation from androgens. Steroidal and non-steroidal inhibitors have successfully been used for treatment of postmenopausal breast cancer and have also been evaluated in clinical studies in patients with endometrial, ovarian cancers and endometriosis. In the last decade also inhibitors of sulfatase that catalyses the hydrolysis of inactive estrogen-sulfates entered clinical trials for treatment of breast, endometrial cancers and endometriosis, with clinical effects seen in breast cancer especially. More recently, inhibitors of 17beta-hydroxysteroid dehydrogenase 1, an enzyme responsible for formation of the most potent estrogen, estradiol, have shown promising results in preclinical studies and have already entered clinical evaluation for endometriosis. This review aims to overview the current status on the use of hormonal drugs for the main hormone-dependent diseases. Further, it aims to explain the mechanisms behind the -sometimes- observed weak effects and low therapeutic efficacy of these drugs and the opportunity and the advantages of combined treatments targeting several enzymes in the local estrogen formation, or drugs acting with different therapeutic mechanism. intracrinology endometrial cancer prostate cancer estrogens breast cancer ovarian cancer endometriosis nosečnice intrakrinologija rak endometrija rak prostate true false true Angleški jezik Slovenski jezik Članek v reviji 2024-01-18 10:13:49 2024-01-18 10:13:54 2024-01-19 03:42:54 0000-00-00 00:00:00 2023 0 0 16 str. art. 1155558 Vol. 14 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 618.1 1663-9812 10.3389/fphar.2023.1155558 150180099 fphar-14-1155558.pdf fphar-14-1155558.pdf 1 2D3C26DD14C776129BBA51EFB373317C 20021ba7caa897ab18dea56aa653f902f2a1b48e8d30c9766d1b0ceaff20dd32 69c3b27a-b5e3-11ee-a699-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=180107 https://www.frontiersin.org/articles/10.3389/fphar.2023.1155558/full 0 4e2a4474-b5e2-11ee-a699-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=180106 Medicinska fakulteta 0 0 0